Our previous studies have suggested that mitochondrial dysfunction causes oxidative genomic DNA damage and contributes to tumorigenesis. Oxygen also serves as an essential substrate for reactive oxygen species formation but it is also essential by aerobic life. We are currently using environmental and genetic methods to modulate oxygen homeostasis and to examine their effect on energy metabolism and tumorigenesis. We are also examining adaptive mechanisms by which cells of neoplastic or cardiovascular origin survive under oxidative or other toxic stress conditions.